TSH Receptor Research Articles

Third-Generation Thyrotropin Receptor Antibody (TRAb) assay for predicting neonatal thyroid dysfunction in pregnant women with Graves' disease.

The aim is to validate the third generation Thyrotropin receptor antibody (TRAb) assay for predicting neonatal thyroid dysfunction and adverse pregnancy outcomes in pregnant women with Graves' disease. This prospective cohort study was conducted in TRAb positive pregnant women with Graves' disease and their off springs. The primary outcome was to assess different forms of neonatal thyroid dysfunction in relation to maternal and neonatal TRAb levels. The secondary outcome was to predict adverse pregnancy outcomes by using maternal TRAb levels. Serum T3, FT4, TSH, TRAb levels were measured using electrochemiluminescence immunoassay. 51 pregnant women were included. Five women had adverse pregnancy outcomes, TRAb levels of > 19.06 IU/L (10.9 times the upper limit of normal (ULN)) predicted adverse pregnancy outcomes with 100% sensitivity and 93.5% specificity. Among the 46 successful live births, 13 (28.3%) had neonatal thyroid dysfunction. Out of 13 neonates, 7 (32%) had neonatal thyrotoxicosis, 4 (18%) had primary hypothyroidism, and 2 (9%) had central hypothyroidism. Third trimester maternal TRAb levels of > 7.99 IU/L (4.6 times the ULN)and day three neonatal TRAb levels of > 5.03 IU/L (2.9 times the ULN), predicted the neonatal thyrotoxicosis with 100% sensitivity and 97.4% specificity. Very high maternal third generation TRAb levels strongly predicted the adverse pregnancy outcomes and neonatal thyroid dysfunction in pregnant women with Graves' disease. Neonatal thyroid function test along with the TRAb levels strongly correlated with different forms of neonatal thyroid dysfunction and is very useful in avoiding inadvertent treatment to neonates.

PREGNANCY OUTCOME IN WOMEN WITH GRAVES’ DISEASE

Background and Aims: Pregnancy complicated with poorly controlled thyrotoxicosis is associated with an increased risk of adverse pregnancy outcomes, and maternal complications. To study the clinical characteristics, feto-maternal outcomes in women with Graves’ disease (GD) during pregnancy. Methods: This was observational study on 98 patients with GD during pregnancy at the tertiary care hospital. GD was documented by Thyrotropin receptor antibody (TRAb). Patients were subjected to complete clinical work up and thyroid profile. The diagnosis of TAO was based on the criteria of Bartley and Gorman. 100 pregnant women with normal thyroid function were taken as control. Birth outcomes recorded were: route of delivery (vaginal or cesarean section), neonatal birth weight, spontaneous abortion, stillbirth, and small for gestational age (SGA). Maternal outcomes accessed were: gestational hypertension, gestational diabetes (GDM), preeclampsia, gestational age at delivery, preterm delivery, antepartum hemorrhage, and postpartum hemorrhage. Results: The mean age of the patients was 30.8±7.6 years as compared to 32.9±6.8 years in controls. Compared with the controls; the pregnant women with GD had significantly higher rates of small for gestational age (SGA) (23.5% vs. 12.0%; p: 0.034), preterm birth (22.4% vs. 12.0%; p: 0.049), preeclampsia (15.3% vs. 5.0%; p: 0.016) and cesarean section (82.7% vs.70.0%; p: 0.036). Maternal and neonatal outcomes in pregnant women with GD with controlled and uncontrolled thyrotoxicosis were not significantly different except for birth weight. Conclusion: GD was significantly associated with an increased risk of adverse pregnancy outcomes.

VASOSPATIC ANGINA IN GRAVES DISEASE

Category A Thyroid hormones play a key role in the growth and metabolism of almost all tissues. Any abnormal increase or decrease of these hormones can cause impairment in functioning of almost all organ systems. Hyperthyroidism has been associated with a number of cardiac manifestations including tachycardia, cardiac arrhythmia especially AF, cardiomyopathy, angina or even myocardial infarction. Here we present a case of a 38 year old female with no known comorbidities who presented to medicine casualty with complaints of recurrent episodes of typical angina lasting 15–20 min or more. Her vitals showed mildly elevated blood pressure of 150/90 mmHg and tachycardia. An ECG taken immediately showed ST segment depression in the anterolateral leads. Cardiac biomarkers were negative. A provisional diagnosis of acute coronary syndrome was made and treatment started. Echo was found to be normal. Patient continued to have recurrent episodes of angina. Coronary angiography was normal. On detailed evaluation patient gave a history of palpitation, loss of weight, diarrhoea and increased sweating in the last 3 months. Detailed physical examination revealed a painless neck swelling. Laboratory tests showed Hb – 12 g/dl, serum K – 4.1 mmol/dl, Ca – 9.2 mg/dl, LFT and RFT normal, fT3 – 22.9, fT4 – 64.2, TSH <0.01 suggestive of hyperthyroidism. On further evaluation she was found to be positive for TSH receptor antibody and was diagnosed with Grave’s disease. She was started on anti-thyroid drugs and propranolol. Nitrates were stopped after 6 months and patient remains asymptomatic on treatment. Conclusion: Hyperthyroidism may present in numerous ways and may even be life threatening. This case highlights the importance of checking the thyroid status of patients, especially in the younger age group, with no obvious cause or risk factors presenting with angina. They may not always have classical symptoms of hyperthyroidism. A delay in diagnosis can result in undue complications and unnecessary interventions. Most of these patients were found to lead a normal life with proper medications once diagnosed.

Perfluorooctanoic acid disrupts thyroid-specific genes expression and regulation via the TSH-TSHR signaling pathway in thyroid cells

Perfluorooctanoic acid (PFOA) is a highly persistent and widespread chemical in the environment with endocrine disruption effects. Although it has been reported that PFOA can affect multiple aspects of thyroid function, the exact mechanism by which it reduces thyroxine levels has not yet been elucidated. In this study, FRTL-5 rat thyroid follicular cells were used as a model to study the toxicity of PFOA to the genes related to thyroid hormone synthesis and their regulatory network. Our results reveal that PFOA interfered with the phosphorylation of the cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB) induced by thyroid-stimulating hormone (TSH), as well as the transcription levels of paired box 8 (PAX8), thyroid transcription factor 1 (TTF1), sodium/iodide cotransporter (NIS), thyroglobulin (TG), and thyroid peroxidase (TPO). However, the above outcomes can be alleviated by enhancing cAMP production with forskolin treatment. Further investigations showed that PFOA reduced the mRNA level of TSH receptor (TSHR) and impaired its N-glycosylation, suggesting that PFOA has disrupting effects on both transcriptional regulation and post-translational regulation. In addition, PFOA increased endoplasmic reticulum (ER) stress and decreased ER mass in FRTL-5 cells. Based on these findings, it can be inferred that PFOA disrupts the TSH-activated cAMP signaling pathway by inhibiting TSHR expression and its N-glycosylation. We propose that this mechanism may contribute to the decrease in thyroid hormone levels caused by PFOA. Our study sheds light on the molecular mechanism by which PFOA can disrupt thyroid function and provides new insights and potential targets for interventions to counteract the disruptive effects of PFOA.

OR26-03 Treatment With Linsitinib, An IGF-1 Receptor Inhibitor, Prevents Disease Development And Progression In An Experimental Model Of Thyroid Eye Disease

Abstract Disclosure: A. Gulbins: Grant Recipient; Self; Sling therapeutics, Inc. M. Horstmann: Grant Recipient; Self; Sling therapeutics, Inc. A. Daser: None. U. Flögel: None. M. Oeverhaus: Grant Recipient; Self; Sling therapeutics, Inc. B.E. Nikolaos: None. J.P. Banga: None. G. Krause: None. G.D. Hammer: Research Investigator; Self; Sling therapeutics, Inc. A.G. Spencer: Research Investigator; Self; Sling therapeutics, Inc. R. Zeidan: Research Investigator; Self; Sling therapeutics, Inc. A. Eckstein: Grant Recipient; Self; Sling therapeutics, Inc. S. Philipp: Grant Recipient; Self; Sling therapeutics, Inc. G. Görtz: Grant Recipient; Self; Sling therapeutics, Inc. Study objective: We investigated the effect of linsitinib, a small molecule inhibitor of the Insulin like growth factor 1 receptor (IGF-1R), on Graves’ disease and thyroid eye disease. Graves‘ disease (GD), also known as “Basedow's disease“, is the most common cause for hyperthyroidism, typically presenting in patients between 40-60 years. GD is an autoimmune condition of the thyroid which is caused by autoantibodies against the thyroid stimulating hormone receptor (TSHR). Thyroid eye disease (TED) is the most common extra thyroidal manifestation of GD and occurs in about 50% of the clinical cases. Methods: To induce Graves’ Disease in mice we immunized mice 3-times with a plasmid encoding for the A-subunit of the TSHR. During each active (early) and chronic (late) states of the autoimmune disease, linsitinib was administered orally for four weeks. Endocrine orbitopathy and inflammation were determined by histology and MRI. Results: As seen in the histology, linsitinib prevented autoimmune hyperthyroidism, morphological changes, formation of brown adipose tissue in the orbita and orbital T-cell and macrophage infiltration into the orbit in the active state as well as the chronic phase. To evaluate the effect of linsitinib during the course of therapy, living mice were examined via MRI. A distinctive migration of immune cells in the orbit with consecutive inflammation can be seen in the TSHR-immunized group, which is completely blocked by treatment with linsitinib. In addition, the orbital inflammation was partnered with the onset of muscle edema and formation of brown adipose tissue in TSHR-immunized mice, effects that were abrogated upon application of linsitinib. Conclusion: In summary, we demonstrate the development of GD and TED in a mouse model upon immunization against the TSHR. The IGF-1R antagonist linsitinib blocks the development of the local pathologies of GD and TED in an early and late phase of the autoimmune disorder and also prevents development of the autoimmune response. We show that treatment of immunized mice with linsitinib after disease onset significantly limited the severity of the disease, indicating the clinical significance of the findings and providing a path to therapeutic intervention of Graves’ Disease. Our data support the use of linsitinib as a novel first line treatment of thyroid eye disease. Presentation: Saturday, June 17, 2023

FRI569 A Therapeutic Dilemma: Spontaneous Oscillating Graves' Disease And Hypothyroidism

Abstract Disclosure: D. Suravajjala: None. J. Case: None. S. Kolli: None. V. Eranki: None. Spontaneous recurrent conversions between hyperthyroidism and hypothyroidism in Graves’ disease (GD) is very rare. We present a case of GD with spontaneous oscillation since diagnosis. From our review, less than 10 cases have been reported in the literature with alternating hyper and hypothyroidism. The patient is a 68-year-old female diagnosed with GD 4 years back with TSH <0.01 (0.4 - 4.5 uIU/mL) and TSI 25.70 (0.00-0.5 IU/L). She denied viral illness, radiation exposure, Lithium or Amiodarone use. Ultrasound thyroid was consistent with GD. Thyroid uptake scan was also consistent with GD. Eventually, Methimazole (MMI) 10 mg daily was initiated. About five months after MMI treatment, she was found to be hypothyroid with TSH 9.030 (0.4-4.5 uIU/mL) and FT4 0.99 (0.9-2.2 ng/dl) which led to discontinuation of MMI. 2 months later, she was clinically hyperthyroid with TSH 0.026, FT4 2.93 (0.9-2.2 ng/dl), TSI 9.59 (0-0.55 IU/L). MMI 5 mg daily was resumed, and as she preferred medical management, other treatment options for GD were not considered. Six months after low dose MMI, patient again reverted to hypothyroidism with TSH 21.420, FT4 0.82. MMI 5 mg was changed to every other day. After 8 months, she was found to be clinically and biochemically hypothyroid with TSH 147, FT4 0.41 (0.9-2.2 ng/dl), TSI 7.98 (0-0.55 IU/L). With the suspicion that she had burnt out GD, she was started on Levothyroxine (LT4) 100 mcg daily. Two months after LT4 initiation, she became clinically hyperthyroid with TSH 0.010 (0.4-4.5 uIU/mL) and FT4 1.91 (0.9-2.2 ng/dl). When trial of LT4 dose reduction failed to alleviate patient hyperthyroid symptoms, it was discontinued and MMI was resumed at 2.5 mg qd. Within 3 months she reverted to hypothyroidism. HAMA interference was as well ruled out. Although the patient's thyroid function ranged spontaneously from hyperthyroidism to hypothyroidism, she was still reluctant for definitive treatment options for GD, including RAI ablation and total thyroidectomy. As GD patients may have definitive treatment early, spontaneous conversion between hyperthyroidism and hypothyroidism is usually not seen in GD and most episodes usually occur several years after discontinuation of antithyroid drugs. It is known that both TSH receptor stimulating antibodies (TSAb) and TSH receptor blocking antibodies (TBAb) can be produced at the same time. The presence of hyper or hypothyroidism may depend on the equilibrium between stimulating and blocking antibodies. Switching of TSH receptor antibodies between stimulation and blockage is uncommon. Diagnosis demands careful clinical and biochemical assessments. Alternatively, the case may be easily mistaken for excessive thyroid suppression or replacement. This condition is difficult to manage, and definitive treatment options could be considered with I-131 ablation, thyroidectomy, or pharmacological treatment (block and replace). Presentation: Friday, June 16, 2023

FRI549 The See-Saw Theory - Hypothyroidism Due To Hashimoto's Thyroiditis Followed By Hyperthyroidism Due To Graves' Disease

Abstract Disclosure: P. Sharma: None. Introduction: Hashimoto's thyroiditis is an autoimmune disorder characterized by chronic inflammation of the thyroid gland that leads to hypothyroidism due to formation of autoantibodies against thyroid antigens such as thyroid peroxidase (TPO Ab). Graves' disease is caused by stimulating TSH-receptor antibodies (TRAb) that cause hypertrophy of the thyroid gland leading to hyperthyroidism. While the transformation of Graves' disease to Hashimoto's thyroiditis has been reported, flipping from Hashimoto's thyroiditis to Graves' disease is uncommon. Case Report: A 62 year old female with 20 year history of hypothyroidism secondary to Hashimoto's thyroiditis presented to establish care. She had run out of levothyroxine refills one year prior during COVID-19 pandemic restrictions. She had tachycardia, diarrhea, fatigue, tremors, hair loss, dysphagia, and weight gain. Thyroid panel testing showed hyperthyroidism with an undetectable TSH (normal range 0.45-4.5uIU/ml) and elevated free T4 (2.84, normal 0.82-1.77ng/ml). Patient denied recent infections, iodine intake or iodine contrast exposure. Repeat labs confirmed hyperthyroidism with undetectable TSH with elevated free T4 (3.17ng/ml). Antibody testing comfirmed hyperthyroidism secondary to Graves disease (TRAb 20.7, normal <1.75IU/L). Patient has been on methimazole with fluctuating response and is reviewing definitive therapy options. Discussion: We demonstrate the rare phenomenon of thyroid function transformation from long-standing inhibition to stimulation after 20 years. Hashimoto's thyroiditis is characterized by chronic inflammation due to autoantibodies against TPO, thyroglobulin and the TSH receptor with gradual gland destruction and hypothyroidism. Stimulating autoantibodies to the TSH receptor (thyroid stimulating immunoglobulin (TSIg), TRAb) in Graves' disease lead to hyperthyroidism from gland hypertrophy. The flip from underactivity to overactivity can be explained by recovery of the gland from Hashimoto's thyroiditis injury which gradually leads to an overt response to TSIg, causing a hyperfunctioning gland. An imbalance between the inhibitory and stimulating antibodies can also lead to this transformation. Age, pregnancy and immunomodulating drugs such as alemtuzumab are also thought to play a role. The recovery theory is unlikely in our patient with a 20 year history of Hashimoto's thyroiditis. We believe that she had a high inhibitory antibody titre initially and now has higher titre of stimulating antibodies later, leading to Graves' disease. Luckily, she ran out of levothyroxine otherwise the additive effect of levothyroxine and intrinsic gland activity could have led to worse symptoms. This case highlights that autoimmune hypothyroidism and hyperthyroidism are conditions in the same spectrum, rather than two distinct entities as previously thought. Presentation: Friday, June 16, 2023

OR26-01 A Novel Small Molecule Thyrotropin Receptor Antagonist

Abstract Disclosure: G.J. Kahaly: None. A. George: None. L. Steiner: None. T. Weirauch: None. J. Henseling: None. L. Frommer: None. J. Wolf: None. Background & aims: Treatment of both Graves’ hyperthyroidism (GH) and Graves’ orbitopathy (GO) is still far from adequate, hence new therapeutic modalities, which specifically target the autoantigens in GH/GO, are warranted. This study determined the preclinical in vitro efficacy of SYD5115, a novel thyrotropin receptor (TSH-R) antagonist. Methods: SYD5115 is a nanomolar potent low molecular weight TSH-R antagonist with in vivo activity in rats after oral dosing. The compound consists of an N-acetylated dihydropyrrole pyrimidine core containing several substituents such as a difluorinated-spirocyclohexyl ring and a chiral carbamate group on the pyrimidine ring. The TSH-R inhibiting capability of SYD5115 was tested through stimulation of wild type and chimeric TSH-R expressed in Chinese hamster ovary (CHO) cells using-two functional (stimulatory and blocking) cell-based TSH-R-Ab bioassays. TSH-R expressing human orbital fibroblasts, collected from GH+GO patients (GOF), were stimulated with the monoclonal antibody M22 or with stimulatory TSH-R-Ab (TSAb)-positive sera with cyclic adenosine monophosphate (cAMP) or hyaluronic acid (HA) release as read-outs. The effect of SYD5115 on the viability of GOF was tested in both 4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide and the “scratch” cell growth assays. Results: The new small molecule SYD5115 significantly and dose-dependently inhibited the TSH-R activation through M22 or TSAb-positive sera in all performed bioassays. Inhibition showed similar levels in the TSAb reporter bioassay and in the cAMP assay with GOF. The % inhibition and compound concentration showed a sigmoidal relationship, with all seven TSAb positive sera markedly inhibited by SYD5115. A SYD5115 dose-dependent inhibition of M22 (10ng/ml, 6 hours)-stimulated HA and/or cAMP-release from GOF was observed. Strong SYD5115-induced inhibitions of M22-stimulated cAMP production in GOF were registered with SYD5115 concentrations of one (p=0.0029), 10 (p<0.0001), 100 (p<0.0001), 1,000 (p<0.0001), and 10,000 (p<0.0001) nM/L, respectively. SYD5115-induced inhibition of M22-stimulated HA production was noted with SYD5115 concentrations of 100 (p=0.0392), 1,000 (p=0.0431), and 10,000 (p=0.0245) nM/L, respectively. The inhibitory activity of SYD5115 was confirmed in a human osteosarcoma U2OS cell line stably expressing human TSH-R with cAMP as read-out. SYD5115 induced 100% inhibition of the M22-induced cAMP levels with a potency of 193 nM. Compared to control, SYD5115 affected neither the growth nor the migration of cultivated GOF. In addition, SYD5115 did not alter the viability of GOF. Conclusions: SYD5115 blocked M22- and TSAb-induced TSH-R activity with a nanomolar potency in TSH-R overexpressed CHO cells as well as primary GOF, which demonstrates the ability of this novel small molecule to inhibit TSH-R overactivity. Presentation: Saturday, June 17, 2023

FRI540 A Novel, Rapid, Sensitive Bioassay For Thyrotropin Receptor Stimulatory Antibodies Improves Diagnosis & Management Of Autoimmune Thyroid Disease

Abstract Disclosure: G.J. Kahaly: None. M.A. Lupo: None. A.T. Bossowski: None. L. Frommer: None. B. Hatun: None. A. George: None. J. Wolf: None. Background: Autoantibody mimicry of hormone action at the thyrotropin receptor (TSH-R) and aberrant signaling of TSH-R by autoantibodies (TSH-R-Ab) causes autoimmune thyroid disease (AITD), hyperthyroidism and hypothyroidism, both of which affect millions of patients worldwide. In this multicenter, single blind study, the specificity, sensitivity and performance of a novel bioassay for stimulatory TSH-R-Ab were tested. Methods: TSH-R-Ab were measured in a blinded manner with a TSH-R binding immunoassay (Cobas e411, Roche), and both stimulatory (TSAb) and blocking (TBAb) bioassays with luciferase release as readout (Thyretain®, Quidel) according to manufacturer’s instructions. TSH-R-Ab was also measured using the new TSAb bioassay (TurboTM). TurboTM utilizes a cAMP biosensor that is an engineered form of firefly luciferase in which the cAMP-binding domain of protein kinase A is fused between the N- and C-termini such that the luciferase is inactive until cAMP binds to the cAMP binding site. Using this biosensor, luciferase activity is proportional to intracellular cAMP levels. TurboTM detects TSAb in serum at room temperature, in a real-time homogeneous format, which delivers results in 60 minutes. It does not require cell culture, sample dilution, washing or cell lysis steps. Results: Eight-hundred forty-four samples of unselected, consecutive AITD patients and control subjects, devoid of autoimmune endocrine and thyroid disorders, were included. Mean age (SD) was 49 (14.7) years, range 1-89 years. Female: male sex ratio was 3.7:1. The four TSH-R-Ab assays were negative in all 174 controls. In contrast, the Turbo TSAb, Thyretain® TSAb and the binding assays detected TSAb in 557 of 670 (83%), 526/670 (78%) and 430/637 (67%) AITD samples, respectively (TurboTM bioassay versus binding immunoassay, chi-square test p<0.001). The results of the Turbo bioassay highly correlated with both thyroid function in Graves’ hyperthyroidism as well as with the clinical activity and severity of associated thyroid eye disease (p<0.001). Inter- (two users) and intra- (two lots) assay comparison for the Turbo bioassay showed coefficient of variations of only 4%, 3%, and 2%, respectively. The two TSAb bioassays, TurboTM and Thyretain®, correlated (Spearman’s r =0.7, p<0.001). Furthermore, the magnitude of serum levels in both TSAb bioassays correlated with TSH-R-Ab binding (both p<0.001). Finally, seventeen AITD samples showed dual TSH-R-Ab positivity in the TBAb and TSAb bioassays. Conclusions: The novel, rapid, easy-to-perform, sensitive and specific TurboTM bioassay performs better than the established TSH-R-Ab binding immunoassay and the Thyretain® bioassay. It provides clinically useful information for the accurate diagnosis and management of AITD patients. Presentation: Friday, June 16, 2023

FRI537 Thyrotropin Receptor Blocking Antibodies - A Multicenter, 4-Assay Comparison

Abstract Disclosure: A. George: None. A.T. Bossowski: None. B. Hatun: None. J. König: None. M.A. Lupo: None. L. Frommer: None. J. Wolf: None. G.J. Kahaly: None. Background: Thyrotropin receptor (TSH-R) blocking autoantibodies (TBAb) are present in 10-15% of patients with autoimmune thyroid disease (AITD). TBAb are functional, impact thyroid function, and are clinically relevant. This multicenter study compares, in a large collective of AITD subjects, the sensitivity and specificity of four immunoassays for the measurement of TBAb and introduces a novel and ultra-rapid TBAb bioassay. Methods: Serum samples from AITD patients were tested with a TSH-R binding immunoassay (Cobas e411, Roche, Penzberg, Germany), an established cell-based TBAb reporter bioassay (Thyretain®, Quidel, San Diego, USA) with expression of a Luciferase transgene as readout and a new “TurboTM” TBAb bioassay (Quidel) with a readout that is based on a cyclic AMP-activated luciferase. A Passing-Bablok regression and intra- and inter-assay validations were performed. All samples were also tested for stimulating TSH-R-Ab (TSAb, Thyretain®, Quidel). Results: Of 1011, unselected, consecutive AITD patients (Graves’ disease and Hashimoto thyroiditis), 132 patients and 212 samples were TBAb positive. Median age was 32 years (25/75 percentile 13.25/46.5 years) and female: male ratio was 2.86:1. Of 212 samples, 149 (70.3%), 47 (23,1%) and 16 (7,5%) were hypothyroid, euthyroid and hyperthyroid, respectively. Thyroperoxidase and thyroglobulin antibodies were present in 136 (64.15%) and 70 (33.02%) samples, respectively. The four TSH-R-Ab assays were negative in 90 control subjects devoid of autoimmune thyroid and endocrine disorders. In contrast, the TurboTM cAMP TBAb, Luciferase TBAb and the Cobas binding assays detected TBAb in 212 (100%), 168 (79%) and 137/180 (76%) samples, respectively (Chi-square test p<0.001). The TurboTM TBAb bioassay highly correlated with thyroid function (p=0.007). Furthermore, the magnitude of percentage inhibition in both TurboTM and Luciferase TBAb bioassays correlated with TSH-R-Ab binding assay positivity (both p<0.001). Seventeen of 212 (8%) samples showed dual TSH-R-Ab positivity in the Turbo TBAb and TSAb bioassays, while 13 (6.1%) samples showed dual positivity for TSAb and TBAb in all three bioassays. The two TBAb bioassays correlated (Spearman’s r =0.59, p< 0.001). Single-user testing and intra-assay validation demonstrated adequate precision with very low coefficient of variation (CV 0.05) and low CV (0.14) at 92% and 44% inhibition (serum TBAb positivity), respectively. Conclusions: This is the largest reported collective of TBAb-positive samples in AITD patients, measured with four different immunoassays. TBAb markedly affects thyroid function. The novel, easy-to-perform, rapid and reliable TurboTM blocking bioassay detected significantly more TBAb than the established immunoassays demonstrating both its higher analytical performance and clinical utility in the management of AITD patients. Presentation: Friday, June 16, 2023

SAT494 Impending Thyroid Storm during Pregnancy in a Patient with Gestational Trophoblastic Disease

Abstract Disclosure: R. Kulkarni: None. Z. Sibai: None. Background: Gestational trophoblastic disease (GTD) is a rare complication of pregnancy that arises due to abnormal proliferation of trophoblasts of the placenta. The incidence of GTD in the United States of America is about 110 to 120 per 100,000 pregnancies. Abnormal trophoblastic proliferation leads to higher than expected B-HCG levels compared to normal pregnancy. Since the beta subunit of β-hCG has similar structure to TSH, β-hCG stimulates TSH receptor and causes hyperthyroidism during pregnancy which can be asymptomatic, mild or it can lead to severe cases of thyroid storm. Clinical Case: A 19-year-old African American woman with no PMH, 8 weeks primigravida presented with complaints of nausea, abdominal pain and difficulty walking. Associated symptoms included blurry vision, excessive sweating, tremors and palpitations. Physical examination finding included sinus tachycardia and low BMIof 18.6kg/m2, bilateral hand tremors, weakness of bilateral lower extremities. Initial labs showed quantitative β-hCG level of 283,163(H) m(iU)/mL, TSH <0.010 (L) m(iU)/L , FT4 2.54 (H) ng/dL, negativeTSI and TPO Abs. Burch-Wartofsky Point Scale score was 35 suggestive of impending thyroid storm. Pelvic ultrasound showed intrauterine pregnancy with estimated gestation age of 7 weeks 3 days with findings suggestive of fetal demise. Patient underwent Dilatation and Curettage for suspected molarpregnancy. Final histopathological report of aborted specimen verified the diagnosis of partial molar pregnancy. Based on clinical history, physical finding and lab results, patient was diagnosed with gestational trophoblastic disease induced impending thyroid storm. Endocrinology initiated management with Propranolol 40 mg TID and Methimazole 10 mg daily withimprovement in her clinical symptoms in two days. One week follow up as an outpatient showed resolution of symptoms, normalization of free T4 and down trending β-hCG titers to 166 m(iU)/mL. Propranolol and methimazole were stopped. Conclusion:Gestational trophoblastic disease although a rare clinical entity, it is potentially a life-threatening condition. β-hCG is a glycoprotein, and its beta subunit is structurally similar to TSH, allowing it to bind to the TSH receptor and causing hyperstimulation of the thyroid follicular cells leading to various degrees of hyperthyroidism. GTD associated with significant high level of β-HCG, in rare cases can cause severe consequences like thyroid storm. Therefore, GTD should be considered as a differential diagnosis in patient’s presenting with sever thyrotoxicosis during pregnancy. The mainstay of management is evacuation of the molar pregnancy. In severe cases of hyperthyroidism, Beta blocker and thioamides can be considered for symptoms relief and to speed the recovery. Follow-up with serial quantitative β-hCG measurements is crucial to evaluate for persistent molar tissue. Presentation Date: Saturday, June 17, 2023

FRI498 Paraneoplastic Hyperthyroidism In A Patient With B-hCG Secreting Gastric Carcinoma

Abstract Disclosure: F. Perreault: None. M. Tehfe: None. M. Laskine: None. L. Ste-Marie: None. R. Comtois: None. B. Nguyen: None. J. Murphy-Lavallée: None. A. Rakel: None. Introduction: Human chorionic gonadotropin (hCG) has thyrotropic activity, due to a similar structure to TSH. Increased hCG serum levels can cause hyperthyroidism secondary to TSH-receptor activation. hCG can be increased in conditions outside of pregnancy, such as gestational trophoblastic disease and other tumors. Common hCG secreting tumors are non-seminomatous germ cell tumors, including choriocarcinoma and teratoma1. Even if gastric adenocarcinomas can secrete ß-hCG, the serum level is rarely elevated2. Clinical Case: A 75-year-old man presented to the hospital for abdominal pain, diarrhea, and important recent weight loss. The patient was known for hypertension, dyslipidemia, type 2 diabetes, and chronic kidney disease. He had been investigated for sub-clinical hyperthyroidism one year prior (TSH 0.27 mUI/L (N 0.38-5.33), T4 14 pmol/L (N 8.0-20.0), T3 4.7 pmol/L (N 3.8-6.0), normal thyroid ultrasound and normal uptake at scintigraphy). At physical examination, the patient looked anxious, had a light lid lag, sinus tachycardia (120 BPM) and a new systolic heart murmur. The thyroid exam was normal and there was no pretibial myxedema nor exophthalmia. The blood tests showed normocytic anemia (Hb 113 g/L, N>130), low TSH (< 0.01 mUI/L), and elevated free T4 (74.1 pmol/L) and T3 (22.5 pmol/L). A work-up for hyperthyroidism revealed normal anti-TPO (4 UI/mL, N<9) and TSH receptor (1.2 UI/L, N<1.8) antibodies levels. Tc-99m thyroid scintigraphy showed homogeneous and intense uptake, with no nodule. Additionally, the abdominal CT-scan revealed multiple retroperitoneal lymphadenopathies and liver hypodensities, suspicious of neoplasia. In this context, the patient underwent gastroscopy, and a gastric antral mass was discovered. Neoplastic markers were measured and, unexpectedly, ß-hCG was strongly elevated (>1 080 800 U/L, N<2.0). Testicle ultrasound was normal. The antral mass biopsy was consistent with infiltrating gastric adenocarcinoma, with ring cells containing intracellular mucin and expressing hCG. The patient was treated with methimazole and propranolol. Free T3 and T4 initially decreased with this treatment (to 7.1 pmol/L and 46.4 pmol/L respectively), but one month later, the serum values were higher (14.9 pmol/L and 69.2 pmol/L). No follow-up was possible for this patient as he passed away before receiving treatment for cancer. Conclusion: ß-hCG induced hyperthyroidism can aggravate patients’ malignant manifestations and should be considered in cases presenting with concomitant cancer and hyperthyroidism.

THU452 Polyostotic Fibrous Dysplasia Complicated By Aneurysmal Bone Cyst In A Patient With McCune-Albright Syndrome

Abstract Disclosure: E. Milazzo: None. K.L. Hermayer: None. Introduction: McCune-Albright Syndrome (MAS) is a rare mosaic disorder with GNAS mutations, encoding the alpha-subunit of the Gs G-coupled protein receptor, activating it, and inappropriately producing cAMP. The hyperfunctioning endocrinopathies associated with MAS are due to signaling through the TSH, LH, FSH, GHRH, and ACTH receptors. MAS clinical presentation occurs with café-au-lait skin macules, precocious puberty, and fibrous dysplasia (FD) of the bone. FD is a benign tumor that leads to increased rates of bone fractures and if it causes facial deformities, can be complicated with orbital neuropathies. An aneurysmal bone cyst (ABC) is a blood-filled cyst that can be a primary or secondary lesion due to co-existing lesions. ABC is a rare complication of FD. We report a rare case of ABC in a MAS patient who presented with acute visual disturbance and enlargement of the forehead and was successfully treated with surgery. Clinical Case: A 20-year-old female diagnosed with MAS at the age of 2 who had precocious puberty by the 3rd year of life and developed polyostotic FD in the right arm, left femur, cranial, and skull bones with multiple long bone fractures by the age of 5-6 and required numerous orthopedic surgeries. She presented with the characteristic café-au-lait skin macules on the back and right arm. In 2018, a slow decline of left eye vision required left cranial decompression of the optic nerve, with pathology showing fibrous tissue compatible with FD. In 2021, she complained of acute right forehead enlargement, compressing her right eye with blurry vision. An MRI showed FD involving the facial and skull bones with a new expansible lesion in the right frontal bone with internal layering fluid, exerting a mild mass effect on the frontal lobe and extending superiorly to the orbit with inferior displacement of the globe. These findings were consistent with an ABC. Right frontal craniectomy and cranioplasty were performed in 12/2021, with pathology showing a fibrous pseudocyst wall with associated lymphoplasmacytic inflammation and evidence of prior hemorrhage with Ki-67 in the cyst wall at 15%. Lab work showed chronic alkaline phosphatase elevation at 567IU/L (42-106IU/L), normal calcium at 9.2mg/dl (8.4-10.3mg/dl), phosphate at 3.3mg/dl (3.3-5.1mg/dl), and PTH at 26pg/ml (15-65mg/dl), with Vitamin D insufficiency at 25.1ng/ml (30-100ng/ml). Endocrinology workup was negative for thyroid, adrenal, gonadotrophic, and GH dysfunction. 5 months post-surgery, the patient demonstrated complete recovery, and MRI showed no recurrence of the ABC. Conclusion: ABC is a benign solitary tumor generally arising from the metaphysis of long bones and rarely involves the cranium. ABC associated with FD has only been reported in a few cases. The treatment is surgical excision, with radiation and cryotherapy used in nonorbital cases. Presentation: Thursday, June 15, 2023

SAT495 Persistent Euthyroid State in a Patient with Biochemical and Imaging Evidence of Graves' Disease

Abstract Disclosure: M. Antony: None. S. Gundlapally: None. M. Joglekar: None. B. Fritz: None. S. Patel: None. V. Verma: None. R. Kant: None. INTRODUCTION: Elevated TSI antibody and/or diffuse uptake on radioactive Iodine-123 scan is diagnostic of Graves’ disease. Thyromegaly with increased blood flow on color doppler seen on thyroid USG can also aid in the diagnosis. Rare presence of positive TSI antibody without hyperthyroidism has been reported1. Rare co-existence of both Graves’ disease and Hashimoto’s thyroiditis in a patient causing a challenging clinical course has been reported2. Presence of a neutralizing or blocking antibody against the TSH receptor1 or a false positive TSI have been implicated in such rare cases. CLINICAL CASE: A 37-year-old Caucasian Female was seen at our endocrinology clinic for further evaluation of thyroid disorder. Patient initially experienced goiter during 1st pregnancy at age 18, followed by hypothyroidism during last pregnancy needing levothyroxine treatment. Due to goiter history, patient underwent work-up by her primary physician in 2021. Thyroid ultrasound (usg) showed bilateral hyperemia, heterogeneous echotexture, and 0.2 cm cystic nodule in the right upper lobe. Labs showed normal TSH 1.33 uIU/ml (0.3-4.0 uIU/ml), normal Free T4 0.99 ng/dl (0.8-1.8 ng/dl), normal total T3 140 ng/dl (71-180 ng/dl). Patient underwent further work-up by endocrinology in 2022. Thyroid ultrasound again revealed bilateral hyperemia with other similar findings. Labs showed normal TSH 2.02uUI/ml, normal free T4 0.93 ng/dl, normal total T3 138 ng/dl. Interestingly, TSI antibody and TPO antibody were significantly elevated at 66.70 IU/L (0.0-0.55 IU/L) and 517 IU/ml (0-34 IU/ml), respectively. Repeat labs in April 2022, again showed normal TSH 1.77 uIU/ml, normal free T4 0.90 ng/dl and normal free T3 2.94 (2.0-4.40 pg/ml). Thyroid uptake scan was not performed due to persistently normal TSH values. Patient denied the use of biotin supplementation. Patient continues to remain clinically and biochemically euthyroid without treatment. CONCLUSION: Our case supports the rare presence of TSI antibody without hyperthyroidism. Close monitoring is warranted due to possibility of future progression to overt hyperthyroidism. REFERENCE: 1. Alvin Mathew A, Papaly R, Maliakal A, et al.(November 10, 2021)Elevated Graves’ Disease-Specific Thyroid-Stimulating Immunoglobulin and Thyroid Stimulating Hormone Receptor Antibody in a Patient With Subacute Thyroiditis. Cureus 13(11): e19448. doi:10.7759/cureus.194482. Vipin Verma, MD, Mc Anto Antony, MD, PSAT346 Persistent Fluctuation Between Hypothyroidism and Hyperthyroidism in a Patient with Both Hashimoto's Thyroiditis and Graves’ Disease: Challenges in Diagnosis and Treatment Approach, Journal of the Endocrine Society, Volume 6, Issue Supplement_1, November-December 2022, Page A833, https://doi.org/10.1210/jendso/bvac150.1723 Presentation Date: Saturday, June 17, 2023

FRI473 Central Hypothyroidism Following Neonatal Graves Presentation

Abstract Disclosure: E. Metzinger: None. K. Halpin: None. Background: Neonatal Graves’ disease is a rare disorder of neonatal autoimmune hyperthyroidism secondary to the transplacental passage of thyroid-stimulating hormone receptor antibodies. Although neonatal Graves’ disease is transient, it is associated with cardiac dysfunction, intrauterine growth restriction, prematurity, craniosynostosis, and developmental delay and can be life-threatening. Additionally, infants with neonatal Graves’ disease can rarely present with primary or central hypothyroidism later in infancy or childhood. This is suspected to be due to the disruption in the hypothalamic-pituitary-thyroid axis or development of the thyroid gland. Clinical Case: Here we describe a case of neonatal Graves’ disease that has been complicated by persistent central hypothyroidism requiring levothyroxine treatment. This was a preterm infant with tachycardia, biventricular heart failure, and hepatomegaly who was transferred to a higher level of care NICU for cardiac and respiratory failure. Pregnancy was complicated by history of maternal Graves’ disease status post radioiodine ablation. Maternal TRAB and thyroid levels were unavailable. Initial thyroid studies on DOL 1 were notable for suppressed TSH of <0.02mcIU/mL, elevated free T4 6.9ng/dL, and elevated total T4 >24.9mcg/dL. Total T3 was normal at 161ng/dL (50-452ng/dL) on DOL 2, and TSI was elevated at 4.8 (TSI Index, normal </= 1.3) on DOL 3. For neonatal thyrotoxicosis, the infant was treated with methimazole, potassium iodide (KI), propranolol, and hydrocortisone. Hydrocortisone was discontinued as the infant clinically improved, and KI was discontinued after 1 week. TFTs were closely followed during admission and methimazole dosing was adjusted as needed. He was discharged from the NICU on DOL 19 on methimazole and propranolol with close outpatient lab monitoring and follow-up. Propranolol was discontinued by 1.5 months of life, and methimazole was discontinued by 2 months of life as TFTs normalized. TSI was negative by four months of life. TSH remained low with decreasing free T4 levels. Ultimately, he was started on levothyroxine at 8.5mcg/kg/day at 2.5 months of age for central hypothyroidism. At that time, TSH was 0.06mcICU/mL and FT4 was 0.7ng/dL. TSH remained low through the first 14 months of treatment with normal free T4 levels on levothyroxine. He has been continued on levothyroxine (average 20mcg/day). Conclusion: This case highlights the severity of neonatal Graves’ disease and the possibility of the subsequent development and persistence of central hypothyroidism following neonatal Graves’ diagnosis despite the resolution of hyperthyroidism and normalization of TSI antibody. Due to the risk of the development of hypothyroidism, it may be worthwhile to continue to trend TSH and FT4 to ensure that the infant has not developed hypothyroidism. Presentation: Friday, June 16, 2023

THU665 Unilateral Graves’ Disease In A Bilobar Thyroid Gland: Unusual Cause Of Hyperthyroidism

Abstract Disclosure: K.H. Alaybaa: None. O. Alhuzaim: None. Introduction: Graves' disease (GD) is an autoimmune condition that affects both thyroid gland lobes. GD patients with unilateral thyroid scan uptake are rare. These patients present with classic Graves' symptoms, occasionally with Graves' ophthalmopathy characteristics and increased thyroid hormones, and scintigraphic assessment reveals radiotracer uptake in only one lobe of the thyroid gland. Patient Findings: In this case, a 48-year-old female presented with symptoms and signs indicative of thyrotoxicosis. Lab results revealed that thyroid-stimulating hormone (TSH) was undetectable, while free thyroxine (T4) and free triiodothyronine (T3) were in the high-normal range. Positive results were observed for both thyroid-stimulating immunoglobulin and TSH receptor antibodies. Ultrasonography of the thyroid gland revealed an enlarged left lobe with heterogeneous echotexture and a hyperemic gland without any focal lesions, distinct nodules, or cysts. The NM TC-99M thyroid scintigraphy revealed enlarged and increased radioisotopes uptake in the left thyroid lobe and decreased uptake in the right thyroid lobe, with no hot or cold nodules. The calculated thyroid uptake is 4.5 percent (normal range: 0.5% to 3.5 percent). The most likely diagnosis was unilateral GD. The patient was administered carbimazole and within eight weeks had improved clinically and biochemically. Summary: This patient has thyrotoxicosis symptoms and positive autoantibodies. Tc99m uptake was increased in the left thyroid lobe and decreased in the right thyroid lobe. The left thyroid lobe was hypervascular and enlarged on ultrasonography, indicating the presence of unilateral GD. Unilateral GD is a rare disease with a poorly understood pathophysiology. Presentation: Thursday, June 15, 2023

FRI568 Hashimoto’s Thyroiditis With Negative Antibodies In Association With Common Variable Immunodeficiency

Abstract Disclosure: I.C. Ebrahim: None. K.F. Brown: None. N.O. Vietor: None. T.D. Hoang: None. M.K. Shakir: None. Introduction: Common variable immunodeficiency (CVID) is associated with several autoimmune manifestations including Hashimoto’s thyroiditis (HT). We report a 47-year-old male with CVID and HT with negative thyroid antibodies (Abs). Case Report: A 47-year-old male, while undergoing coronary calcium scan in 2021, was found to have scattered lung nodules. Follow-up Ct scans showed interval increase in size of lung nodules and a PET scan confirmed bilateral lung nodules which demonstrated hypermetabolic activity and scattered hypermetabolic lymph nodes, suggesting infectious or inflammatory processes. PET scan also revealed thyromegaly with diffusely increased uptake, suggesting thyroiditis. Serum immunoglobulins were measured: IgA < 5 mg/dL (normal 70-400), IgG 334 mg/dL (normal 700-1600), and IgM < 25 mg/dL (normal 40-230). Serum immunoglobulins levels from depository serum samples collected in 2005 also showed similarly low values. CBC was normal, excluding any bone marrow disorders. There was no family history of immunodeficiency or thyroid disorders. On review of systems patients did not have any symptoms of hypothyroidism. Exam: thyroid 50-gms diffusely enlarged with no palpable nodules; heart and lung exam was normal. Laboratory tests including comprehensive metabolic panel, serum complement CH 50, leukemia/lymphoma panel, T/B - lymphocyte/Natkiller, CRP were all normal. Thyroid functions: TSH 5.6 mc1U/mL (0.27-4.2), Free T4 1.20 ng/dL (0.93-1.71), TPO Ab < 9 IU/mL (0-34), TG Ab < 1.0 1U/mL (0.0-0.9), thyrotropin receptor Ab < 0.3 IU/L (<1.0), thyroid stimulating immunoglobulin < 0.10 1U/L (0.06-0.55). Serum thyroid Ab levels from depository samples collected in 2005 also showed normal values. FNA of thyroid showed atypical lymphoid infiltrates and an excision biopsy of the thyroid isthmus confirmed lymphocytic thyroiditis. A PET avid right inguinal lymph node biopsy showed a reactive lymph node. Additional lab evaluation also showed low post vaccination pneumococcal titers. With pan-hypoglobulinemia and low vaccine response, a diagnosis of CVID was made. Patient preferred watchful waiting than iv immunoglobulin therapy. Additionally, the patient has HT with negative thyroid Abs and although patient had mild subclinical hypothyroidism patient elected no treatment. Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency in adults. Autoimmune manifestations occur in 22% of CVID patients and these include autoimmune cytopenia, pernicious anemia, rheumatoid arthritis, vitiligo, and/or HT. Interestingly, our patient did not manifest any thyroid Abs thus it may be postulated that thyroid follicles destruction in HT is mediated predominantly by thyroid-specific B and T cells rather than by thyroid antibodies. Presentation: Friday, June 16, 2023

THU655 Methimazole Desensitization As An Effective Alternative To Ablation Therapy In Patients With Graves’ Disease Experiencing Thionamide-induced Type IV Hypersensitivity Reactions

Abstract Disclosure: J. Arguinchona: None. A. Mahajan: None. A. Gonzalez-Estrada: None. E. De Filippis: None. Introduction: Patients with newly diagnosed Graves’ disease often choose treatment with methimazole (MMI) over traditional ablation therapies. However, MMI can result in adverse reactions including skin rash, pruritus, and urticaria. We present a case of Graves’ thyrotoxicosis with a type IV hypersensitivity reaction while on MMI. The patient was successfully treated with a novel, individualized, 27-day desensitization protocol which resulted in tolerance of MMI with subsequent improvement in thyroid indices. Clinical Case: A 42-year-old female presented for abnormal thyroid studies with associated insomnia, heat intolerance, palpitations, resting tremor, and weight loss. Lab work revealed a thyroid-stimulating hormone <0.005 (0.450-4.500 μIU/mL), free thyroxine 3.28 (0.82-1.77 ng/dL), triiodothyronine 310 (71-180 ng/dL), thyroid peroxidase antibody (Ab) 62 (0-34 IU/mL), thyroid-stimulating immunoglobulin 0.67 (0.00 -0.55 IU/L), and thyrotropin receptor Ab of 6.00 (0.00-1.75 IU/L). She was started on MMI, 10 mg daily for Graves’ disease. Three weeks later, T3 and T4 remained elevated prompting an increase in MMI dose to 10 mg twice daily. Two weeks later, she developed a diffuse, pruritic maculopapular exanthema over her trunk, neck, and extremities. Methimazole was discontinued while prednisone was initiated that subsided her rash. Unfortunately, the patient’s symptoms recurred upon repeat MMI exposure. The patient declined propylthiouracil due to concerns of hepatotoxicity and elected to avoid ablation therapy with iodine or surgery. With the assistance of an allergist, a novel, 10-step, 27-day desensitization protocol was developed specifically for her reaction to MMI with plans to taper prednisone once desensitization was completed. The patient underwent desensitization with development of mild lower extremity exanthema that was successfully treated with high dose antihistamines. Three months later, she was tolerating MMI at 15 mg daily without further adverse reactions and tapered off prednisone. While on MMI, her immune titers normalized with euthyroid clinical and biochemical restoration. Conclusion: Many patients and clinicians initially prefer medical management over definitive ablation therapies in the treatment of Graves’ disease. This case demonstrates with the assistance of an allergist, desensitization to MMI is a viable option in the setting of a known hypersensitivity reaction when it is the first line treatment and no equally efficacious alternatives exist. In addition, patient’s preferences should also be considered during medical decision making. Previous literature has offered various rapid desensitization protocols for MMI for immediate type hypersensitivity reactions. However, in non-immediate, type IV hypersensitivity reactions, a slower desensitization protocol can be considered, as demonstrated in this case. Presentation: Thursday, June 15, 2023

SAT553 A Case of Metastatic Functional Papillary Thyroid Cancer in the Setting of Graves’ Disease

Abstract Disclosure: N. Manuel: None. S.J. Sternlieb: None. J. Dendy: None. Q.Z. Iqbal: None. A Case of Metastatic Functional Papillary Thyroid Cancer In the Setting of Graves’ DiseaseManuel, N., Sternlieb, S., Grissett, B., Iqbal, Q., Dendy, J. Background: Grave’s disease (GD) and papillary thyroid cancer (PTC) can be concomitant diseases. We report a rare case of metastatic PTC with concomitant GD leading to symptomatic hyperthyroidism despite total thyroidectomy. Clinical Case: A 58-year-old woman with longstanding history of thyroid nodules and left dominant nodule with benign biopsy on multiple occasions presented to her PCP with dyspnea, weight loss and globus sensation. CT of the chest was obtained revealing tracheal deviation from neck mass, mediastinal lymphadenopathy and multiple pulmonary nodules. Biopsy of lung nodule showed follicular features consistent with tumor cells of thyroid origin. She had a total thyroidectomy with central neck dissection with a final diagnosis of left sided 5 cm infiltrative follicular variant papillary thyroid carcinoma. Thyroid hormone replacement was initiated and on follow up 4 weeks later she was noted to be tachycardic at weight-based dose. At that time TSH was <0.010 uIU/mL (0.400 - 4.00), free T4 was 1.96 ng/dL (0.71 – 1.51) and Thyroglobulin was found to be 31516 ng/dL (Athyrotic <0.1). Prior to planned RAI she developed symptoms of dyspnea on exertion and edema and was sent to the ER for abnormal D. Dimer. Workup for PE was negative including CTA of the chest. A follow up visit showed further symptoms of hyperthyroidism with worsening fatigue, dyspnea, palpitations and new onset tremor. Levothyroxine dose was decreased further but 2 weeks later she returned to the ER with worsened thyroid function tests, and she was admitted for symptomatic hyperthyroidism. Levothyroxine was held and she was placed on PTU and propranolol. Given the overt symptomatic hyperthyroidism there were concerns for either Jod-Basedow phenomenon from iodine load with recent imaging or for hyperfunctioning PTC metastasis as the cause. Thyrotropin receptor antibody level was checked to further clarify and was elevated at 22 IU/L (0.00 – 1.75) consistent with GD. An I-131 diagnostic whole-body scan demonstrated small foci of right thyroid bed remnant and iodine-avid metastases involving mediastinal nodal disease as well as pulmonary and osseous metastases. She then underwent RAI therapy with 104.5 mCi I-131 without Thyrogen stimulation. Follow up whole body scan showed persistence of iodine-avid metastasis without any new foci of uptake compared to pretreatment scans. Conclusion: Although the coexistence of them is rare, GD should be put into the differential of rapidly progressive metastatic PTC especially if patient markedly hyperthyroid on lower doses of thyroid hormone. While functional thyroid carcinoma is rare, with less than 100 cases in literature, thorough investigation should be completed in order to not miss this concomitant disease process. Presentation Date: Saturday, June 17, 2023

FRI512 Thyrotoxic Periodic Paralysis With Extreme Hypokalemia Precipitated By Acute Alcohol Intoxication In A Patient With Graves’ Disease

Abstract Disclosure: J. Batra: None. A.R. Ankireddypalli: None. J. Kaur: None. Introduction: Thyrotoxic periodic paralysis (TPP) is a muscle and electrolyte disorder, mostly seen in the setting of hyperthyroidism. It is characterized by reversible painless muscle weakness and hypokalemia. Prevalence is highest in East Asian populations, approximately 2%, and 0.1-0.2% in other populations. Males are much more likely to be affected. Common provoking factors include exercise, fasting, and changes in diet. Clinical case: A 29-year-old male of East Asian ethnicity presented to the hospital with the complaint of multiple bouts of inability to lift his extremities for 1 day. He also complained of generalized weakness. He did not have any changes in his mental status and was fully oriented at the time of the presentation. No breathing difficulty was reported. He had been drinking the night before with his friends and drank 1 L of vodka. His past medical history was significant for hyperthyroidism secondary to Graves’ disease, which was diagnosed a year ago. He had been prescribed methimazole but had not been adherent to the medication. The basic metabolic panel revealed undetectable serum potassium of <1.5 (3.4 to 5.3 mmol/L). The rest of the electrolytes and renal function were unremarkable. TSH was suppressed at <0.01 (0.3 to 4.20 uIU/L) and free T4 levels were significantly elevated at 7.77 (0.9 to 1.70 ng/dL). The thyrotropin receptor antibody was 33 (0.00 to 1.75 IU/L). EKG showed sinus tachycardia with nonspecific T-wave abnormalities. Thyroid ultrasound showed diffusely heterogenous parenchyma with diffusely increased blood flow throughout the thyroid on doppler. Echocardiogram showed a normal ejection fraction of 55-60% with mild concentric left ventricular wall thickening consistent with left ventricular hypertrophy. He was initially treated with intravenous potassium replacement and high doses of propylthiouracil, hydrocortisone, and propranolol, leading to the resolution of his symptoms. He was discharged on methimazole and propranolol therapies. Learning points: • Patients with Graves’ disease are routinely counseled against tobacco use to avoid worsening of orbitopathy. Hyperthyroid patients should also be counseled regarding avoidance or moderation of alcohol intake to avoid this rare but potentially life-threatening complication of thyrotoxic periodic paralysis. • The incidence of TPP is significantly higher in the East Asian populations, especially among males (8.7-13%). Counseling regarding provoking factors, the importance of adherence to medications, and the maintenance of euthyroidism to avoid TPP is essential. Presentation: Friday, June 16, 2023